This invention relates to a novel process for the preparation of .alpha.-haloacetoacetic esters by the reaction of an alkali metal alkoxide with a 5-halo-4H-1,3-dioxin-4-one compound.
The preparation of acetoacetic esters by the reaction of alcohols and diketene in the presence of an acid catalyst has been described by A. B. Boese in Ind. Eng. Chem. 32, 16 (1940). The sodium enolate salt of ethyl acetoacetate has been reported by Chick et al, Journal of American Chemical Society 93, 946 (1908) and 97, 1978 (1910) to be produced by reacting diketene and sodium ethoxide in dry alcohol. The desired .alpha.-halogenated product may be obtained by treating the acetoacetic ester with a suitable halogenating agent, e.g. SO.sub.2 Cl.sub.2. [See Boehme, Org. Syn. Coll., Vol. 4, 590 (1963)].
Reported by Blomquist et al in Journal of American Chemical Society, Vol. 70, page 29 (1948) is the preparation of ethyl 2-bromoacetoacetate by first treating ketene dimer in chloroform solution with N-bromosuccinimide followed by reaction with ethyl alcohol. The 2-chloro derivative was similarly prepared by treating ketene dimer with N,2,4-trichloroacetanilide followed by reaction with ethyl alcohol. Reported yields are 43% and 35%, respectively.
An alternate method has now been found for producing .alpha.-haloacetoacetic esters. According to this process, .alpha.-haloacetoacetic esters are obtained from 5-halo-4H-1,3-dioxin-4-ones by the reaction thereof with an alkali metal alkoxide.
By this process various .alpha.-haloacetoacetic esters may be obtained using a common starting material. The product is advantageously obtained as an enolate salt which affords protection of the halogen from displacement. In addition, the 5-halo precursor is obtained without the use of expensive halogenating agents. The process is particularly advantageous for halogen-sensitive alcohols since the halogen moiety is introduced prior to ring opening of the dioxinone compound. While 1,3-dioxin-4-one compounds such as 2,2,6-trimethyl-4H-1,3-dioxin-4-one are known to react in a manner similar to diketene in many reactions, reacting sodium ethoxide with the aforementioned dioxinone does not give ethyl acetoacetate. Surprisingly 4H-1,3-dioxin-4-one compounds which contain Cl or Br at the 5-position of the dioxinone ring do react with alkali metal alkoxides to give acetoacetic esters monohalogenated at the .alpha.-position.